Long Reads Versus More Reads:
Comparing Two Sequencing Tools for Evaluating Live Biotherapeutics as Microbiome Interventions
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A longstanding challenge in microbiome research has been achieving the taxonomic resolution needed to generate testable hypotheses about how the gut microbiome impacts human health and disease, and to assess the mechanism and efficacy of specific microbiome interventions. Short read whole genome shotgun metagenomic sequencing provides high taxonomic resolution plus functional information but is expensive for large cohort studies. Because of its lower cost, short-read sequencing of the bacterial 16S rRNA gene has become the standard for microbiome profiling, despite its limitations.
Recently, HiFi sequencing with PacBio has offered an alternative to both short-read shotgun metagenomics and partial 16S gene sequencing, providing richer information from shotgun data and higher taxonomic resolution from full length 16S sequences. Here, we use 12 human microbiome samples from 6 donors enrolled in a Phase 1b trial of a live biotherapeutic product to compare the utility and cost effectiveness of long-read and short-read sequencing methods for evaluating microbiome interventions using both 16S StrainID from Shoreline Biome and PacBio HiFi sequencing shotgun datasets.
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Meredith Ashby, Ph.D.
Director, Strategic Marketing
Jeanette Gehrig, Ph.D.